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Form and Function of Tandem Duplicate Small RNA Molecules in Shigella dysenteriae

痢疾志贺氏菌串联重复小 RNA 分子的形式和功能

基本信息

批准号：
8574164
负责人：
ERIN R MURPHY
金额：
$ 44.55万
依托单位：
OHIO UNIVERSITY ATHENS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-16 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8574164
关键词：
Achievement Antibiotic Resistance Antibiotics Attention Bacteria Biological Assay Cell division Communicable Diseases Computer Simulation Data Development Disease Dysentery Environment Equilibrium Foundations Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Transcription Goals Human Human body Incidence Infection Infection prevention Invaded Iron Knowledge Mediating Mentors Modeling Molecular Nutrient Pathogenesis Pathway interactions Pattern Phenotype Physiology Play Positioning Attribute Process Production RNA Regimen Regulation Research Role Shigella Shigella Infections Shigella boydii Shigella dysenteriae Shigella flexneri Small RNA Structure Students System Temperature Testing Therapeutic Training Training Programs Vaccines Virulence Water antimicrobial drug bacterial genetics base commensal microbes experience human disease innovation model development novel therapeutics pathogen pathogenic bacteria prevent public health relevance response skills

项目摘要

DESCRIPTION (provided by applicant): Shigellosis, a several diarrheal disease caused by infection with bacteria of the genus Shigella, remains endemic throughout the world. The global burden of shigellosis is due in part to the lack of a vaccine to prevent the infection and the lack of a universally safe and available antibiotic regimen to treat the infection. While the potential f using small RNA molecules (sRNAs) as models for, or targets of, RNA-based anti-Shigella therapeutics is promising, what is lacking is a comprehensive understanding of the role that sRNAs play in controlling Shigella physiology and pathogenesis. A necessary first step towards achieving the long-term goal of developing RNA-based antibiotics to treat shigellosis is to reveal the full extent to which sRNAs control the physiology and virulence of Shigella species. To this end, the overall objective of this study is to elucidate the role of newly identified duplicate sRNAs RyfA1 and RyfA2 in controlling the physiology and pathogenesis of S. dysenteriae. The central hypothesis being tested is that RyfA1 and RyfA2 are differentially produced under unique environmental conditions and modulate S. dysenteriae virulence by regulating the expression of distinct over-lapping sets of genes. This hypothesis will be tested by achieving the following specific aims: 1) identify the iron- and temperature-responsive factors regulating the production of RyfA1 and RyfA2; 2) elucidate the function of RyfA1 and RyfA2 by identifying the regulatory targets of each; and 3) determine the effect of RyfA1 and RyfA2, individually and in combination, on S. dysenteriae virulence. The proposed systematic characterization of duplicate sRNAs, RyfA1 and RyfA2, will contribute to answering fundamental questions in the fields of Shigella pathogenesis and bacterial sRNAs, contributions that will facilitate achievement of the long-term goal of developing therapeutics to treat shigellosis. The proposed study puts forth the innovative hypothesis that two sRNA molecules that share 95% sequence identity and a identical predicted structure have non-redundant functions. This hypothesis will be tested using a balanced approach of standard, student friendly, bacterial genetics and innovative high-tech assays. Student involvement in every step of the proposed study form the foundation of an innovative training program that will provide students with practical experience in the fields of bacterial pathogenesis and RNA-based regulation. The resulting combination of skills and experience will position students well to contribute to the rapidly advancing fields of ribo-regulation in pathogenic bacteria, commensal bacteria and eukaryotic systems.

描述（由申请人提供）：志贺氏菌病是一种由志贺氏菌属细菌感染引起的几种腹泻疾病，在世界各地仍然流行。志贺氏菌病的全球负担部分是由于缺乏预防感染的疫苗和缺乏